Prostaglandin E2 (hereinafter referred to as “PGE2”) is known as one of the metabolites in an arachidonic acid cascade. The PGE2 exhibits various activities, for example, a pain inducing and increasing action, a pro-inflammatory action, an anti-inflammatory action, an uterine contractile action, a digestive peristalsis promoting action, an awaking action, a gastric acid secretion inhibiting action, a hypotensive action, a platelet aggregation inhibition action, a bone resorption-promoting action, an angiogenic action, and the like.
There exist four subtypes, EP1, EP2, EP3, and EP4, for the PGE2 receptors, which have a wide distribution in various tissues. The activation of the EP1 receptor is believed to cause the increase in intracellular Ca2+. The EP3 receptor is one of the receptors having different routes for second-messenger systems. The activation of the EP2 and EP4 receptors is believed to cause the activation of adenylate cyclase, and thus to increase the intracellular cAMP level. In particular, it is believed that the EP4 receptor is related to relaxation of smooth muscles, promotion or inhibition of an inflammatory reaction, lymphocyte differentiation, hypertrophy or proliferation of mesangial cells, secretion of gastrointestinal mucus, and the like.
An inhibitor of a PGE2 receptor, that is, a PGE2 antagonist has a binding activity to the PGE2 receptor. That is, the PGE2 antagonist exhibits a PGE2 antagonistic activity or a PGE2 inhibitory activity. Accordingly, the PGE2 antagonist is expected to be a drug for treating diseases caused by PGE2. Among these, the EP4 receptor antagonist is expected to be an agent for treating EP4-related diseases, for example, renal disease, inflammatory diseases, various pains, and the like, in human and animals. In addition, the antagonist selective to the EP4 receptor is preferred from the viewpoint that it can avoid the side-effects based on the subtypes of other EP1, EP2, and EP3.
As an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 1).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor ligand, a compound represented by the following formula is known (Patent Document 2).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 3). In this connection, this document was published after the priority date of the present application.

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 4).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 5).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 6).

(For the symbols in the formula, refer to this publication.)
Further, as EP4 receptor ligands, compounds represented by the following formulae are known (Patent Document 7).

(For the symbols in the formulae, refer to this publication.)
Further, as an EP3 and/or EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 8).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor blocker, a compound represented by the following formula is known (Patent Document 9).

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 10). In this connection, this document was published after the priority date of the present application.

(For the symbols in the formula, refer to this publication.)
Further, as an EP4 receptor antagonist, a compound represented by the following formula is known (Patent Document 11). In this connection, this document was published after the priority date of the present application.

(For the symbols in the formula, refer to this publication.)